Embryonic stem cell transplants as a therapeutic strategy in a rodent model of autism

Jennifer J. Donegan, Angela M. Boley, Daniel J. Lodge

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Autism is a neurodevelopmental disorder characterized by disruptions in three core behavioral domains: deficits in social interaction, impairments in communication, and repetitive and stereotyped patterns of behavior or thought. There are currently no drugs available for the treatment of the core symptoms of ASD and drugs that target comorbid symptoms often have serious adverse side effects, suggesting an urgent need for new therapeutic strategies. The neurobiology of autism is complex, but converging evidence suggests that ASD involves disruptions in the inhibitory GABAergic neurotransmitter system. Specifically, people with autism have a reduction in parvalbumin (PV)-containing interneurons in the PFC, leading to the suggestion that restoring interneuron function in this region may be a novel therapeutic approach for ASD. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of PV-positive interneurons, which were transplanted into the medial prefrontal cortex (mPFC) of the Poly I:C rodent model of autism. PV interneuron transplants were able to decrease pyramidal cell firing in the mPFC and alleviated deficits in social interaction and cognitive flexibility. Our results suggest that restoring PV interneuron function in the mPFC may be a novel and effective treatment strategy to reduce the core symptoms of autism.

Original languageEnglish (US)
Pages (from-to)1789-1798
Number of pages10
JournalNeuropsychopharmacology
Volume43
Issue number8
DOIs
StatePublished - Jul 1 2018

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ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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